Cleft lip with or without cleft palate (CL/P) are very common structural birth defects. CL/P is predominantly sporadic in occurrence and about 22 percent of patients with facial clefts have a genetic origin. Linkage analysis and/or association studies have allowed narrowing down several candidate regions, but not sufficiently to indicate likely candidate genes for re-sequencing from patients. The goal of this proposal is to survey the genome for candidate regions by searching for micro-deletions/duplications and to compare the relative efficacy of this approach with the more conventional genetic association studies to identify candidate genes for CL/P. Our approach is based on comparative genomic hybridization (CGH) using very-high resolution BAG arrays to screen for genomic segments involved in copy-number changes. The specific aims are to: (1) Perform array CGH from 200 patient DNA samples over 2 years; (2) Identify sporadic deletions/duplications possibly shared between multiple patients; (3) Search for candidate genes from the common deletion region through public databases. (4) Confirm alleged genomic rearrangements in a representative set of samples by fluorescent in situ hybridization of BACs to the chromosomes from patients and parents.